Brief Summary: This phase II trial studies how well administering ruxolitinib before, during, and after allogeneic hematopoietic stem cell transplantation works in preventing graft versus host disease and improving transplant outcomes in patients with primary and secondary myelofibrosis. Donor hematopoietic stem cell transplantation (HSCT) is currently the only treatment with proven curative potential for myelofibrosis, however, myelofibrosis patients have a high risk for developing graft versus host disease post-transplant. Graft versus host disease is a condition where the transplanted cells from a donor can attack the body's normal cells. Ruxolitinib, a janus-associated kinase (JAK) inhibitor, is known to decrease inflammatory signals, which may reduce spleen size and decrease symptoms such as night sweats and weight loss. Administering ruxolitinib before, during, and after transplant may decrease the incidence and severity of graft versus host disease, increase survival, and improve quality of life in patients with primary and secondary myelofibrosis.

Detailed Description: OUTLINE: PART 1: Patients receive ruxolitinib orally (PO) starting 8 weeks prior to hematopoietic stem cell transplantation (HSCT) and continuing until approximately 14 days prior to conditioning regimen, then tapered per the treating clinician until day -4 in the absence of disease progression or unacceptable toxicity. Patients who join a different research study for Part 2 have their collected data and samples from Part 1 carried over to the new protocol. PART 2: Patients are assigned to either a high (myeloablative) or reduced intensity conditioning regimens per the clinical provider together with the Clinical Coordinators Office (CCO): MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide intravenously (IV) on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2. Patients with umbilical cord blood (UCB) as their transplant source also receive fludarabine IV over 30 minutes on days -8 to -6. Treatment continues in the absence of disease progression or unacceptable toxicity. REDUCED INTENSITY CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. Patients with UCB as their transplant source also undergo total body irradiation (TBI) on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity. TRANSPLANT: After completion of conditioning regimen, patients undergo HSCT on day 0. GVHD PROPHYLAXIS: Patients receive ruxolitinib until approximately 7 months post-transplant and then tapered over 2 months until 9-12 months post HSCT. Patients also receive tacrolimus IV continuously (inpatients) or every 12 hours (outpatients) beginning day -1 (day -3 for patients with UCB as their donor source), then PO twice daily (BID) once therapeutic levels are reached, with a taper beginning on day 56 for patients with related donors, and day 100 for patients with unrelated donors over 4 months in the absence of GVHD. The duration of tacrolimus for patients with GVHD is determined by the attending physician. Patients with related and unrelated donors also receive methotrexate IV on days 1, 3, 6, and 11. Patients with UCB as their transplant source also receive mycophenolate mofetil IV or PO every 8 hours beginning on days 0-30, then tapered until day 40 in the absence of GVHD. All treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and may undergo echocardiography on study and bone marrow aspiration and biopsy and blood sample collection and may undergo magneti resonance imaging (MRI) and ultrasound throughout the study. Patients are followed up at 6 months, 1 year, and 2-5 years after completion of HSCT.